诊断试验(英文)课件

1、诊断试验(英文)诊断试验(英文)Diagnostic test are not just about diagnosisScreeningDetermining severityOptimally therapyPrognosisMonitor Diagnostic test are not just aExampleCarotid ultrasound can tell you the severity of the patients carotid stenosis Carotid ultrasound can tell you the patients prognosis for str

2、oke and deathCarotid ultrasound can predict your patients likely responsiveness to therapyExampleCarotid ultrasound can Basic principles of conducting diagnostic studiesApply the gold standard to determine whether or not the target condition is present Gold standard: The most recognized standard for

3、 clinician to diagnose the target conditionPathological measurementOperation findingSpecial imaging detectionLong-term follow-up Recognized standardBasic principles of conductingWhat if your test is more gold than the standardMay lead to underestimate of the diagnostic power of the evaluatingOne str

4、ategy for dealing with this problem is to use long-term follow-up as a gold standardWhat if your test is more goldTo Whom Should the Gold Standard Be Applied?to everyoneselective performing the gold standard on patients may result in “ verification bias ” or “workup bias”To Whom Should the Gold Stan

5、daRecruit your participantsRecruit the target-negative and target-positive participants identified by gold standard characteristic of those to whom you will want to apply the test in clinical practiceIncluding a broad spectrum of the diseasedcase：from mildly to severelycontrol：a broad spectrum of co

6、mpeting conditionsAn alternative approach is that recruiting a consecutive sample of patientsRecruit your participantsRecru诊断试验(英文)诊断试验(英文)Measurement proceduresSpecifying test techniqueReproducibilityBlinding of the individual conducting or interpreting the test to the gold standardMeasurement proc

7、eduresSpecifyiSelect statistical procedureCalculating sample sizeSelect statistical procedureCa Example: Assuming a sensitivity of 80%, specificity of 60% of ultrasonography for diagnosis of cholecystolithiasis. How many samples are needed ? Example: Assuming a sensitiResult evaluation indexExample:

8、 126 patients underwent independent, blind BNP measurement and echocardiography for diagnosis of LVD.Result evaluation indexExample诊断试验(英文)sensitivity：a/(a+c)=35/40=0.88, or 88%specificity：d/(b+d)=29/86=0.34, or 34%positive predictive value (PPV)：a/(a+b)=35/92=0.38, or 38%negative predictive value (

9、NPV)：d/(c+d)=29/34=0.85, or 85%prevalence: (a+c) / (a+b+c+d)=40/126=0.32, or 32%Pre-test odds: pre-test probability/(1- pre-test probability) =32% / 68%=0.47positive likelihood ratio ( LR+ ): Sen/1-Spe=88% /(100%-34%)=1.3sensitivity：a/(a+c)=35/40=0.88诊断试验(英文)Multilevel likelihood ratiosMultilevel li

10、kelihood ratiosStability of the indexStable : Sen, SpeRelatively stable: LR+, LR- Unstable : PPV, NPV, prevalence:Stability of the indexStable :Receiver operating characteristic curves(ROC)It illustrates the performance of a diagnostic test when you select different cut-points to distinguish “normal

11、” from “abnormal” It demonstrates the fact that any increase in sensitivity will be accompanied by a decrease in specificityThe closer the curve gets to the upper left corner of the display, the more the overall accuracy of the testThe closer the curve comes to the 45-degree diagonal of the ROC spac

12、e ,the less accurate the testThe area under the curve provides an overall measure of a tests accuracyReceiver operating characteris Fig A ROC for BNP as a diagnostic test for LVD Fig A ROC for诊断试验(英文)Parallel test A test B test Result + + + + + + + -Parallel test A test Reduction miss diagnosisExclu

13、de some disease When prevalence is low, as the primary screening methodReduction miss diagnosisSerial test A test B test Result + + + + - + - -Serial test A test Sen = Sen A SenBSpe = Spe A + (1-Spe A) Spe BMisdiagnosis may cause nuisance effect Confirmatory diagnosis Sen = Sen A SenBSpe = Spe A Ser

14、ial test with enzyme labeled compound assay for diagnosis of myocardial infarctionEnzyme labeled compound assaySenSpeCPK9657SGOT9174LDH879191Serial test with enzyme labelMultivariate analysisSEN SPEMultivariate analysisSEN single variable analysismarkermethodsSEN (%)spe (%)cutoffAREAaELISA90.788.80.

15、19150.926bELISA77.373.20.20350.802cELISA74.270.90.09050.762dELISA78.481.61.080.836eELISA90.784.40.3560.932fELISA84.581.60.7990.899 single variable analysismarkemultivariate analysis using logistic regression Combined markersSEN（）SPE（）AREAa and b88.882.50.926a and c87.782.50.927a and e91.690.070.974a

16、 and f95.590.070.967a and d87.285.6.0936b and c78.876.30.837b and d87.786.60.934b and e83.882.50.900b and f82.781.40.863C and d87.785.60.946C and e88.385.60.926C and f81.679.40.854d and e89.486.60.946d and f88.386.60.952e and f87.785.60.933multivariate analysis using loPrediction the probability of

17、a diseaseLogit(P)= -0.934+4.797 x a +2.203 x ePrediction the probability of Avoiding overfitting Overfitting occurs when a computer model identifies a “chance” pattern that discriminates cancer patients from non-cancer patients, perfectly fitting that dataset but not reproducible in other data sets.

18、One way to avoiding overfitting is to randomly split the data into separate training and test samples.Avoiding overfitting OverfThe EBM steps for diagnostic testsLooking for the most suitable study papers according to the clinical questionBring forward the question in clinicExample 2 : if detection

19、of serum forritin can diagnose Iron deficiency anemia?Search the computer information using the apposite key word“diagnose Iron deficiency anemia” and “diagnostic test” and “human”The EBM steps for diagnostic tEvaluation of the scientificity of the papersIf compared with the gold standard independen

20、tly and blindlyExample 2: Iron stain with myeloid biopsyEvaluation of the scientificitIf detected with the control test for every quizzeeGold standardTotal （No.）Results+-New diagnostic test +351550sensitivity=46%New diagnostic test -40460500specificity=96.8%If detected with the control Verification

21、biasGold standardTotal （No.）Results+-New diagnostic test +3515 50sensitivity=90%New diagnostic test -446 50specificity=75%Verification biasGold standardIf the patient samples included a broad spectrum of the diseaseIf the disease spectrum uniform Whats the objective question that the investigator co

22、ncerned aboutIf the study sample and the quizzee is uniformSpectrum bias：overstate the performance parameter of the diagnostic test because of excluding the “grey zone” patientsIf the patient samples includeThe precision of the diagnostic tests Definition: in the same condition, degree of stability

23、of achieving the same result when repeating the operation Detailed introduction the procedurestandards of reporting diagnostic accuracy, STARDThe precision of the diagnostiEstimate the significance of clinical applicationEstimate the pre-test probabilityPre-test probability：Estimating the suffering

24、probability before diagnostic testMedical recordMedical examination Individual experience Epidemiology dataEstimate the significance of cThe predictive value depend on the pre-test probability of illnessThe predictive value depend onExplain and use of sensitivity and specificityHigh sensitivity test

25、 (negative test, rule out)High specificity test (positive test, rule in )Explain and use of sensitivityUse likelihood ratio, LRLikelihood ratio： provides a direct estimate of how much a test result will change the probability of having a diseaseLR+ = sensitivity/(1- specificity)Likelihood ratio unch

26、anged with the prevalence rate Overcoming deficiency with only sensitivity or specificity to expressUse likelihood ratio, LRLikelipost-test probability post-test probability = post-test odds / （1 + post-test odds ）post-test odds = pre-test odds LR pre-test odds = pre-test probability （1- pre-test pr

27、obability ）Crude principle: LR 10 or 0.1 affirm or denial 5 LR 10 or 0.1 LR 0.2 moderate probability 2 LR 5 or 0.2 LR 0.5 minor probability 1 LR 2 or 0.5 LR 100 81080.13denial45-100 7270.45minor probability18-45 23133.10moderate probability=18 47242.5 affirmTotal 85150The LR with serum ferritin forThe LR with serum ferritin for diagnosis of iron-deficiency anemiaThe LR with serum ferritin